Treatment with FHD-286 depletes MEP cells and reduces chromatin accessibility and enrichment scores of MYC TARGET genes in the CMP cluster of PD mtNPM1 + FLT3-ITD expressing AML cells. (A) PD mtNPM1-expressing AML cells from a bone marrow aspirate were treated with 100 nM of FHD-286 for 16 hours. Multiomics (combined sc-ATAC-Seq and sc-RNA-Seq) analyses were performed on isolated nuclei. The uniform manifold approximation and projection (UMAP) plot shows the SingleR-determined composition of the individual cell clusters in the control and FHD-286-treated AML cells. (B) Percentage of each cell type in the clusters of cells from control and FHD-286–treated cells. Arrows indicate clusters with increased or decreased numbers of cells in the FHD-286–treated sample compared with the control sample. (C) Volcano plot of sc-ATAC-Seq peaks in the CMP cluster with ≥1.25-fold change up or down and P value <.05 after treatment with FHD-286. (D) Gene set enrichment analysis of FHD-286–treated cells over control cells. All q-values are <0.1. (E) Volcano plot of sc-RNA-Seq expression changes (≥1.25 fold change and P < .05) in the CMP cluster after treatment with 100 nM FHD-286 for 16 hours compared with control cells. CMP, common myeloid progenitor; MEP, megakaryocyte-erythroid progenitor.